Linked Life Data

12081208

Source:http://linkedlifedata.com/resource/pubmed/id/12081208

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-6-25
pubmed:abstractText
Post-transcriptional modification of p53 by phosphorylation has been proposed to be an important mechanism of p53 stabilization and functional regulation. Phosphorylation of p53 Ser392, in particular, activates specific DNA binding functions by stabilizing p53 tetramer formation. This study evaluated the relationship between p53 Ser392 phosphorylation and various types of p53 missense mutation detected in urothelial transitional cell carcinomas (TCCs), with stratification of the mutations according to the functional domains elucidated by the crystal structure of the p53 protein. Of 41 TCCs with missense mutations, 26 (63.4%) exhibited immunopositivity with Ser392 phospho-specific p53 antibody. In comparison to structural mutations, the missense mutations at exon 7 (p=0.0307) or located in regions that affect direct DNA binding ability (p = 0.0273) were significantly associated with Ser392 immunopositivity. No statistically significant relationship was found between Ser392 immunoreactivity and other different types of p53 mutation. The prevalence of cases exhibiting Ser392-positive immunostaining was higher for high-grade (p <0.0001) and advanced-stage TCCs (p =0.0119) than for TCCs with wild-type p53. No significant relationship was found between Ser392 immunoreactivity and apoptotic index in urothelial TCCs. These in vivo findings indicate that Ser392 phosphorylation frequently occurs in mutant form p53 in TCCs. Because mutant form p53 can act dominant-negatively by heterooligomerization with wild-type p53, these findings also suggest that Ser392 phosphorylation might activate tetramer formation to promote the dominant-negative effects of mutant form p53, and thereby contribute to proliferation of aggressive TCCs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-3417
pubmed:author
pubmed:issnType
Print
pubmed:volume
197
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
82-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Frequent phosphorylation at serine 392 in overexpressed p53 protein due to missense mutation in carcinoma of the urinary tract.
pubmed:affiliation
Department of Pathology II, Kochi Medical School, Nankoku, Japan. furihata@kochi-ms.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't